The most common cause of pheochromocytoma is sporadic mutations. Less common causes of pheochromocytoma include familial associations and association with syndromes. Familial pheochromocytoma may be caused by a mutation of either SDHD, VHL, SDHB, RET, NF1 genes.

• Pheochromocytoma due to any cause may be life-threatening which may result in death.

• In most cases of pheochromocytoma, the cause is unknown.
• Sporadic form is more common

Less common causes of pheochromocytoma include:

• Familial form
• Associated with syndromes- Neurofibromatosis 1, Von Hippel-Lindau disease, Multiple Endocrine Neoplasia 2A and 2B

Pheochromocytoma of the familial type may be caused by a mutation in the following genes:

• RET gene (MEN 2A, MEN 2B syndromes)
• NF1 gene
• VHL gene (VHL disease)
• SDHD, SDHB, and SDHC genes of the mitochondrial complex ^[1]
• SDHA, SDHAF2, TMEM127 (transmembrane protein 127), MAX (myc-associated factor X), FH (fumarate hydratase), PDH1, PDH2 (pyruvate dehydrogenase), HIF1alpha (hypoxia-inducible factor), MDH2 (malate dehydrogenase), and KIF1Bß (kinesin family member) genes. ^[2]

Pheochromocytoma and paragangliomas (PPGL) susceptibility genes can be classified into the following clusters- ^{[3] [4] [5]}

• Cluster 1
  • Mutations involving in overexpression of vascular endothelial growth factor (VEGF) as a result of pseudohypoxia
  • Impaired DNA methylation leading to increased vascularization
• Cluster 2
  • Activating mutations of Wnt-signaling pathway including Wnt receptor signaling and Hedgehog signaling.
  • Mutations of CSDE1 (Cold shock domain containing E1) and MAML3 (Mastermind like transcriptional coactivator 3) genes7.
• Cluster 3
  • Abnormal activation of kinase signaling pathways like PI3Kinase/AKT, RAS/RAF/ERK, and mTOR pathways.

List of causes of the disease in alphabetical order: